B7-H1 molecule increases the apoptosis of tumor-reactive T lymphocytes and reduces their immunogenicity. Breast cancer is the second most common cause of mortality after lung cancer. Direct evidence linking B7-H1 with cancer has been shown in several malignancies; however, its expression in breast cancer has not been investigated. We used immunohistochemistry to investigate the expression of the B7-H1 molecule in 44 breast cancer specimens and to study its correlation with patients' clinicopathological parameters. The expression of B7-H1 was shown in 22 of 44 patients and was not restricted to the tumor epithelium (15 of 44, 34% in tumor cells), but was also expressed by tumor-infiltrating lymphocytes (TIL; 18 of 44, 41%). Interestingly, intratumor expression of B7-H1 was significantly associated with histologic grade III-negative (P = .012), estrogen receptor-negative (P = .036), and progesterone receptor-negative (P = .040) patients. In addition, the expression of B7-H1 in TIL was associated with large tumor size (P = .042), histologic grade III (P = .015), positivity of Her2/neu status (P = .019), and severe tumor lymphocyte infiltration (P = .001). Taken together, these data suggest that B7-H1 may be an important risk factor in breast cancer patients and may represent a potential immunotherapeutic target using monoclonal antibody against the B7-H1 molecule.

B7-H1, a coinhibitory molecule, plays a role in immune escape of tumors. We have shown previously the expression of this molecule in breast cancer patients and demonstrated its association with high histological grade, progesterone and estrogen receptor negative status, all of which are known to have direct impact on cell proliferation. In the present work, we investigated the effect of proliferation, as measured by Ki-67 and mitotic count, on the induction of B7-H1. We used H&E stained sections to score for mitotic count in 69 breast cancer patients. Immunohistochemistry was used to investigate B7-H1 and Ki-67 expression. The relationship between B7-H1 induction and cell proliferation was further investigated in primary cultured cells. B7-H1 expression was recorded in patients with a high mitotic index (p 5 0.007). There was a high significant correlation between B7-H1 expression and the presence of the proliferative marker Ki-67 (p < 0.001) indicating the association of proliferation with B7-H1 induction. Furthermore, B7-H1 was gradually induced in proliferating cells of 8/8 primary cell lines as measured by Ki-67 expression. Finally, B7-H1 was downregulated in quiescent cells and upregulated in cells stimulated with a mitogen confirming the association of proliferation with the induction of B7-H1. We have shown for the first time a direct association between proliferation and the expression of B7-H1 in breast cancer patients. The relationship between B7-H1 induction and cell proliferation was also thoroughly investigated in vitro, in which a strong link between B7-H1 expression and the presence of the proliferative Ki-67 marker was clearly demonstrated. ' 2007 Wiley-Liss, Inc.Key words: B7-H1; PD-L1; breast cancer; Ki-67; proliferation; mitotic index About 40% of women still die of breast cancer in spite of the significant advances in traditional, targeted and neo-adjuvant therapies. 1 Immunotherapeutic strategies aimed at manipulating the patient's immune system to specifically destroy tumor cells may represent a major alternative approach for the management of cancer. 2,3 However, the presence of an existing immune tolerance in patients with advanced cancer may limit the clinical effectiveness of such therapeutic strategies. 4 Several mechanisms have been attributed to the immune defect seen in breast cancer patients with advanced disease; where a lower number of blood lymphocytes, 5 elevated T regulatory lymphocytes, 6 defective dendritic cells 7 and expression of FasL in breast cancer 8 were described.A T lymphocyte inhibitory molecule named B7-H1 (also called PD-L1) expressed by antigen presenting cells has been shown to induce T lymphocyte anergy and/or apoptosis after ligation to its T lymphocytes receptor PD-1. 9-12 It has been shown to be directly involved in the protection of cancer cells from activated T lymphocytes. 13 The expression of this molecule has been described in several malignancies including ovary, colon, melanoma and carcinoma of the lung. 11 Others includes; squamous cell carcinoma o...

Heart failure is associated with the reactivation of a fetal cardiac gene programme that has become a hallmark of cardiac hypertrophy and maladaptive ventricular remodelling, yet the mechanisms that regulate this transcriptional reprogramming are not fully understood. Using mice with genetic ablation of calcium/calmodulin-dependent protein kinase II δ (CaMKIIδ), which are resistant to pathological cardiac stress, we show that CaMKIIδ regulates the phosphorylation of histone H3 at serine-10 during pressure overload hypertrophy. H3 S10 phosphorylation is strongly increased in the adult mouse heart in the early phase of cardiac hypertrophy and remains detectable during cardiac decompensation. This response correlates with up-regulation of CaMKIIδ and increased expression of transcriptional drivers of pathological cardiac hypertrophy and of fetal cardiac genes. Similar changes are detected in patients with end-stage heart failure, where CaMKIIδ specifically interacts with phospho-H3. Robust H3 phosphorylation is detected in both adult ventricular myocytes and in non-cardiac cells in the stressed myocardium, and these signals are abolished in CaMKIIδ-deficient mice after pressure overload. Mechanistically, fetal cardiac genes are activated by increased recruitment of CaMKIIδ and enhanced H3 phosphorylation at hypertrophic promoter regions, both in mice and in human failing hearts, and this response is blunted in CaMKIIδ-deficient mice under stress. We also document that the chaperone protein 14–3–3 binds phosphorylated H3 in response to stress, allowing proper elongation of fetal cardiac genes by RNA polymerase II (RNAPII), as well as elongation of transcription factors regulating cardiac hypertrophy. These processes are impaired in CaMKIIδ-KO mice after pathological stress. The findings reveal a novel in vivo function of CaMKIIδ in regulating H3 phosphorylation and suggest a novel epigenetic mechanism by which CaMKIIδ controls cardiac hypertrophy. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Primary pleural angiosarcomas are extremely rare. As of 2010, only around 50 case reports have been documented in the literature. Herein, we report the case of a 63-year-old gentleman who presented with a 3-month history of right-sided chest pain, dyspnea, and hemoptysis. Chest X-ray showed bilateral pleural effusion with partial bibasilar atelectasis. Ultrasound-guided thoracocentesis showed bloody and exudative pleural fluid. Cytologic examination was negative for malignant cells. An abdominal contrast-enhanced computed tomography (CT) scan showed two right diaphragmatic pleural masses. Whole-body positron emission tomography/computed tomography (PET/CT) scan showed two hypermetabolic fluorodeoxyglucose- (FDG-) avid lesions involving the right diaphragmatic pleura. CT-guided needle-core biopsy was performed and histopathological examination showed neoplastic cells growing mainly in sheets with focal areas suggestive of vascular spaces lined by cytologically malignant epithelioid cells. Immunohistochemical analysis showed strong positivity for vimentin, CD31, CD68, and Fli-1 markers. The overall pathological and immunohistochemical features supported the diagnosis of epithelioid angiosarcoma. The patient was scheduled for surgery in three weeks. Unfortunately, the patient died after one week after discharge secondary to pulseless ventricular tachycardia arrest followed by asystole. Moreover, we also present a brief literature review on pleural angiosarcoma.

Mesenchymal hamartoma of the chest wall is a well-recognized but extremely rare entity. This entity is believed to be benign with no propensity for invasion or metastasis. Although the lesion manifests with alarming aggressive clinical, radiological, and histological features, it is considered benign and carries an excellent outcome. Therefore it is important to recognize this benign entity to avoid the possible misdiagnosis of malignancy and the unnecessary use of chemotherapy. We present a case of bilateral multifocal mesenchymal hamartomas of the chest wall in a male infant and a literature review of this entity. Our aim is to improve the awareness of this condition and highlight its benign behavior and satisfactory outcome following complete surgical resection.